Significant progress was made in the development of a live attenuated RSV subgroup A vaccine by introducing additional attenuating mutations into mutants, such as cpRSV, that were not completely attenuated for fully susceptible humans. Several promising candidate RSV subgroup A vaccine candidates were produced and evaluated. The cpts 248/955, 248/404, and 530/1009 mutants derived from cpRSV were selected from a large panel of mutants for further study because they were attenuated, stable genetically, immunogenic, and able to induce protection in rodents or chimpanzees. Importantly, these mutants were able to induce a high level of resistance to wild type virus challenge even in chimpanzees passively infused with RSV antibodies at the time of immunization, a situation that simulates that of the young human infant whose serum usually contains passively acquired maternal RSV antibodies. The nucleotide sequence of the most promising attenuated viruses is being determined while that of the cpRSV parent mutant was completed this year. The cpts248/955 virus was found to be highly stable genetically in seronegative humans, but was not completely attenuated in these infants and young children. Importantly, the cpts530/1009 mutant appeared to be satisfactorily attenuated and stable genetically in the seven infected vaccinees evaluated thus far. The cpts530/1009 vaccine is our most promising candidate to date for the subgroup A component of a bivalent RSV vaccine. Progress toward the development of the subgroup B component of the bivalent RSV vaccine was also made this year. It appears that the cpRSV B1/2B5 candidate vaccine virus sustained three independent mutations that contributed to its attenuation for cotton rats. The attenuation phenotype of this mutant was highly stable even after prolonged replication in immunosuppressed cotton rats. Derivatives of the cpRSV B1/2B5 mutant were obtained following mutagenesis and two further attenuated ts mutants were identified, namely cpRSV B1 176 and cpRSV B1 176/427. Both components of a bivalent subgroup A and B vaccine were able to replicate in vivo without apparent interference.